Maltreated foster youth experience severe adversities and disruptions that place them at risk for substance use disorders (SUD) and related health risk behaviors, making them an important target for prevention. The negative squeal of SUD in this vulnerable population is exacerbated by multiple disadvantages and a paucity of resources as they transition to adulthood, compounding the effects for them and for society. Yet our ability to prevent SUD for this population continues to be sharply limited by a poor understanding of why some current and former foster youth progress to SUD and others do not. Multiple developmental perspectives suggest that preventing progression to SUD among foster youth requires the identification of context-specific risk and protective processes with high salience to the particular circumstances of foster care. The proposed research will use an innovative mixed methods design (qualitative/ quantitative) to achieve a better understanding of context-specific risk and protective processes that affect developmental trajectories of drug use, including progression to SUD, among current and former foster youth, and explore how differences in identified processes influence youth transition to adulthood. We will use existing quantitative data from the Consortium of Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) - including rich multi-informant data collected every two years from age 4 through 18 and coded CPS maltreatment records - and will collect new qualitative data with 40 participants from LONGSCAN's unique Southwest site cohort (n = 330), all of whom were placed in foster care by the age of three and a half years due to substantiated maltreatment. Growth mixture modeling of drug use at ages 12, 14, 16, and 18 will be used to identify a purposeful sample of participants who exhibit distinct drug use trajectories, stratified by placement history to permit comparison between groups. Semi-structured interviews using a modified critical incident technique will capture (a) individual cognitive, emotional, and behavioral responses, (b) positive and negative relationship processes, and (c) co-occurring exposures to multiple adversities during three theoretically meaningful transitional periods with high salience for foster youth: transitions (1) between placements and caregivers; (2) from drug use to SUD; and (3) from adolescence to adulthood. Results from qualitative and quantitative analyses will inform the development of a conceptual model of the development of SUD from early childhood through early adulthood for youth who have experienced foster care. Hypotheses generated by the new model will be tested in a follow-up study on SUD, risk behaviors, and adjustment in the transition to adulthood. This study and the R01 that will build on it are highly responsive to PA-11-231, which calls for research with diverse populations on the origins and trajectories of drug use, abuse, and addiction, including progression to SUD and transitions from adolescence to adulthood, and to NIDA's strategic goals of learning how adverse childhood experiences influence drug abuse vulnerability and developing knowledge that leads to customized treatments.